HISTOLOGICAL CHARACTERIZATION OF PLACENTA IN …...Gordijn SJ. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab

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HISTOLOGICAL CHARACTERIZATION OF PLACENTA IN COVID19PREGNANT WOMEN

Fulvia Milena Cribiu

PII: S0301-2115(20)30416-4

DOI: https://doi.org/10.1016/j.ejogrb.2020.06.041

Reference: EURO 11448

To appear in: European Journal of Obstetrics & Gynecology and ReproductiveBiology

Giorgio Alberto Croci

PII: S0301-2115(20)30416-4




Alessandro Del Gobbo, Tommaso Rizzuti

PII: S0301-2115(20)30416-4




https://doi.org/10.1016/j.ejogrb.2020.06.041



Enrico Iurlaro, Marta Tondo, Anna Viscardi

PII: S0301-2115(20)30416-4




Silvano Bosari

PII: S0301-2115(20)30416-4




Stefano Ferrero

PII: S0301-2115(20)30416-4




Received Date: 28 April 2020

Please cite this article as: Cribiu FM, Croci GA, Gobbo AD, Rizzuti T, Iurlaro E, Tondo M,Viscardi A, Bosari S, Ferrero S, HISTOLOGICAL CHARACTERIZATION OF PLACENTA INCOVID19 PREGNANT WOMEN, European Journal of Obstetrics and amp; Gynecology and




Reproductive Biology (2020), doi: https://doi.org/10.1016/j.ejogrb.2020.06.041

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© 2020 Published by Elsevier.


Letter to the editor – brief communication

HISTOLOGICAL CHARACTERIZATION OF PLACENTA IN COVID19 PREGNANT WOMEN

Fulvia Milena Cribiù, MD1*; Giorgio Alberto Croci, MD1,3*; Alessandro Del Gobbo, MD1;

Tommaso Rizzuti, MD1; Enrico Iurlaro, MD4; Marta Tondo, MD4; Anna Viscardi, MD4; Silvano

Bosari, MD1; Stefano Ferrero, MD1,2.

From: 1Division of Pathology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico,

Milan, Italy; 2Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan,

Italy; 3Department of Department of Pathophysiology and Transplantation, University of Milan,

Milan, Italy; 4Department of Women's and Children's Health, University of Milan and Fondazione

IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy.

* equally contributed

CORRESPONDING AUTHOR

Alessandro Del Gobbo

Division of Pathology

Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico

Via Francesco Sforza, 35

20122 Milan, Italy

e-mail: [email protected] – tel.: +390255038494 – fax: +390255032860

Dear Editor,

The outbreak of SARS-CoV2 infection between the end of 2019 and the beginning 2020 has

now involved most of the countries and represents a global challenge for health management (1).

Pregnant women are considered a susceptible category because of the limited data on

maternal and neonatal outcomes of pregnant women with SARS-CoV2 infection (1).

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In viral infections, histological examination of the placenta usually shows lesions that are

characteristic for the different types of viruses with overlapping features.

This is a descriptive study of histological alterations in a series of placenta from pregnant

women with documented SARS-CoV2 infection.

Nine patients who delivered between March and April 2020 at Fondazione IRCCS Ca’ Granda –

Ospedale Maggiore Policlinico (Milan), with SARS-CoV2 infection documented by

nasopharyngeal swab test were enrolled in this study. Clinicopathological characteristics are shown

in Figure 1 – Table section.

Clinically, one case (case #4) presented with fever up to 37.5° C and cough and another case (case

#9) suffered from fever up to 38,5° C and bilateral interstitial pneumonia documented by chest X-

ray which conditioned a severe respiratory distress; the remaining cases were asymptomatic.

Five histological samples for each case were paraffin-embedded and stained with

Haematoxylin & eosin including umbilical cord sections, amnio-chorial membranes, and three

sections of the parenchyma.

The histochemical staining Giemsa and PAS and the immunohistochemical staining for CD3,

CD20, CD4, CD8, CD14, CD15, CD31 were performed to evaluate the inflammatory infiltrate and

the structural alterations.

Reports were in accordance with the recently published guidelines (2).

Maternal vascular malperfusion of the placental bed

Distal villous hypoplasia was detectable in 2 out of 9 cases (22%), with a variation in villous

diameters, formation of villous clusters, distal and peripheral villous hypoplasia. There was fewer

fetal arterioles and those remaining showed hypertrophy of the media.

Distal villous immaturity was seen in association with distal villous hypoplasia, with an

increased number of enlarged distal villi, stromal cells and villous macrophages.

Delayed villous maturation

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Five/9 cases (55%) showed a delayed villous maturation that is characterized by a

monotonous population of chorial villi with a reduction in the number of syncytial vascular

membranes as well as the presence of a continuous coating of cytotrophoblasts and central

capillaries in the villi.

Perivillous fibrin deposits, calcifications and intimal hyperplasia of truncular and

intermediate vessels were present in 8/9 (88%), 6/9 (67%) and 4/9 (44%) cases, respectively.

Other lesions

One case showed villous immaturity and one presented meconium on the chorial plate, free

or incorporated in macrophages.

In one case, a leukocitoclasic vasculitis without evidence of vascular thrombi in small,

medium and terminal villi and with acute intervillitis was found.

Immuno- and histochemical results

No significant T- and B-cell infiltrate was observed.

Only one case, with Giemsa staining, showed focal changes related to thrombotic vascular disease

in a vascular malperfusion background.

Our results show the high rate of chronic hypoxy-related morphological alterations of the

placental parenchyma such as delayed villous maturation associated with perivillous fibrin deposits,

calcifications and intimal hyperplasia.

One case (case #5) displayed a marked infiltration of the vascular tree by neutrophils and

lymphocytes, with the characteristics of acute vasculitis.

During labour just two fetuses suffered from alterations in the cardiotocogram, one of them

also with a reduction of the fetal movements. The Apgar scores of the newborn babies was of 9 and

10 at 5 and 10 minutes in most of the cases, newborn and placental weights were coherent for

gestational age and all the newborn swap test were negative, predicting a good outcome of the

pregnancies and indicating that there was no evidence of vertical transmission of SARS-CoV2 from

infected pregnant mothers to newborns.

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In conclusion, our results are like those showed in the only one reported study in literature

and available in PubMed regarding placenta morphological analysis from SARS-CoV2 infected

women, where no specific histological alterations were detectable (3-5), as these finding are

common in other maternal conditions such as gestational diabetes or hypertension. Further studies

will be needed to best understand the possible role of placenta in a potential vertical transmission

and in the clinical outcome of the newborns.

AUTHOR CONTRIBUTIONS

Fulvia Milena Cribiù and Giorgio Alberto Croci drafted the manuscript, Enrico Iurlaro, Marta

Tondo and Anna Viscardi provided and analyzed clinical data, Alessandro Del Gobbo and

Tommaso Rizzuti analyzed histological data, Silvano Bosari, Stefano Ferrero revised the

manuscript and supervised the work.

CONFLICTS OF INTEREST

The authors declare they have no conflicts of interest.

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that

could have appeared to influence the work reported in this paper.

REFERENCES

1. Zaigham M, Andersson O. Maternal and Perinatal Outcomes with COVID-19: a systematic

review of 108 pregnancies. Acta Obstet Gynecol Scand. 2020 Apr 7. doi:

10.1111/aogs.13867

2. Khong TY, Mooney EE, Ariel I, Balmus NC, Boyd TK, Brundler MA, Derricott H, Evans

MJ, Faye-Petersen OM, Gillan JE, Heazell AE, Heller DS, Jacques SM, Keating S, Kelehan

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P, Maes A, McKay EM, Morgan TK, Nikkels PG, Parks WT, Redline RW, Scheimberg I,

Schoots MH, Sebire NJ, Timmer A, Turowski G, van der Voorn JP, van Lijnschoten I,

Gordijn SJ. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop

Group Consensus Statement. Arch Pathol Lab Med. 2016;140.

3. Karimi-Zarchi M, Neamatzadeh H, Dastgheib SA, Abbasi H, Mirjalili SR, Behforouz A,

Ferdosian F, Bahrami R: Vertical transmission of Coronavirus Disease 19 (COVID-19)

from infected pregnant mothers to neonates: a review. Fetal Pediatr Pathol. 2020 Apr 2:1-5

doi : 10.1080/15513815

4. Chen S, Huang B, Luo DJ, Li X, Yang F, Zhao Y, Nie X, Huang BX. Pregnant women with

new coronavirus infection: a clinical characteristics and placental pathological analysis of

three cases. Zhonghua Bing Li Xue Za Zhi. 2020 Mar 1;49(0):E005.

doi:10.3760/cma.j.cn112151-20200225-00138.

5. Mulvey JJ, Magro CM, Ma LX, Nuovo GJ, Baergen RN. Analysis of complement

deposition and viral RNA in placentas of COVID-19 patients. Ann Diagn Pathol. 2020 Apr

25;46:151530. doi: 10.1016/j.anndiagpath.2020.151530.

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Figure 1 – Morphological alterations of the placenta: (A) Perivillous calcification associated with

perivillous and intravillous fibrin deposits (H&E, original magnification: 100x); (B) villous

immaturity, characterized by loose reticular stroma with capillaries in the center of the villi (H&E,

original magnification: 100x); (C and D) Acute intervillitis, characterized by marked neutrophils

infiltrate in the perivillous space, highlighted with anti-CD15 immunohistochemical staining (C,

H&E, original magnification: 50x and D, anti-CD15 antibody (Dako®), original magnification:

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100x); (E and F) Acute leukocytoclasic vasculitis, with neutrophils migrating from the lumen to the

vessel wall, better shown with histochemical Giemsa staining (E, H&E, original magnification:

100x and F, Giemsa, original magnification: 100x, case #5); (G) Chronic recanalized arthery with

marked hypertrophy of the wall (H&E, original magnification: 100x); (H) A small cluster of

thrombotic villi, with fibrotic and avascular stroma (H&E, original magnification: 100x).

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HISTOLOGICAL CHARACTERIZATION OF PLACENTA IN …...Gordijn SJ. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab